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Home > Anti-aging Research > NADH

Nicotinamide adenine dinucleotide (NAD+)

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  • Oral nicotinamide riboside raises NAD+ and lowers biomarkers of neurodegenerative pathology in plasma extracellular vesicles enriched for neuronal origin - Aging Cell 2022 Dec 14 - "Declining nicotinamide adenine dinucleotide (NAD+ ) concentration in the brain during aging contributes to metabolic and cellular dysfunction and is implicated in the pathogenesis of aging-associated neurological disorders. Experimental therapies aimed at boosting brain NAD+ levels normalize several neurodegenerative phenotypes in animal models, motivating their clinical translation. Dietary intake of NAD+ precursors, such as nicotinamide riboside (NR), is a safe and effective avenue for augmenting NAD+ levels in peripheral tissues in humans, yet evidence supporting their ability to raise NAD+ levels in the brain or engage neurodegenerative disease pathways is lacking. Here, we studied biomarkers in plasma extracellular vesicles enriched for neuronal origin (NEVs) from 22 healthy older adults who participated in a randomized, placebo-controlled crossover trial (NCT02921659) of oral NR supplementation (500 mg, 2x /day, 6 weeks). We demonstrate that oral NR supplementation increases NAD+ levels in NEVs and decreases NEV levels of Aβ42, pJNK, and pERK1/2 (kinases involved in insulin resistance and neuroinflammatory pathways). In addition, changes in NAD(H) correlated with changes in canonical insulin-Akt signaling proteins and changes in pERK1/2 and pJNK. These findings support the ability of orally administered NR to augment neuronal NAD+ levels and modify biomarkers related to neurodegenerative pathology in humans. Furthermore, NEVs offer a new blood-based window into monitoring the physiologic response of NR in the brain" - See nicotinamide riboside at Amazon.com.
  • Nicotinamide mononucleotide alleviates osteoblast senescence induction and promotes bone healing in osteoporotic mice - J Gerontol A Biol Sci Med Sci 2022 Aug 29 - "Combating the accumulated senescent cells and the healing of osteoporotic bone fracture in the elderly remains a significant challenge. Nicotinamide mononucleotide (NMN), a precursor of NAD +, is an excellent candidate for mitigating aging-related disorders. However, it is unknown if NMN can alleviate senescent cell induction and enhance osteoporotic bone fracture healing. Here we show that NMN treatment partially reverses the effects of tumor necrosis factor-alpha (TNF-α) on human primary osteoblasts (HOBs): senescent cell induction, diminished osteogenic differentiation ability and intracellular NAD + and NADH levels. Mechanistically, NMN restores the mitochondrial dysfunction in HOBs induced by TNF-α evidenced by increased mitochondrial membrane potential and reduced reactive oxidative species and mitochondrial mass. NMN also increases mitophagy activity by down-regulating P62 expression and up-regulating light chain 3B-II (LC3B-II) protein expression. In addition, the cell senescence protective effects of NMN on HOBs are mitigated by a mitophagy inhibitor (Bafilomycin A1). In vivo, NMN supplementation attenuates senescent cell induction in growth plates, partially prevents osteoporosis in an ovariectomized mouse model and accelerates bone healing in osteoporotic mice. We conclude that NMN can be a novel and promising therapeutic candidate to enhance bone fracture healing capacity in the elderly." - See NMN at Amazon.com.
  • Supplementation with NAD + and Its Precursors to Prevent Cognitive Decline across Disease Contexts - Nutrients 2022 Aug 7 - "The preservation of cognitive ability by increasing nicotinamide adenine dinucleotide (NAD+) levels through supplementation with NAD+ precursors has been identified as a promising treatment strategy for a number of conditions; principally, age-related cognitive decline (including Alzheimer's disease and vascular dementia), but also diabetes, stroke, and traumatic brain injury. Candidate factors have included NAD+ itself, its reduced form NADH, nicotinamide (NAM), nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and niacin (or nicotinic acid). This review summarises the research findings for each source of cognitive impairment for which NAD+ precursor supplementation has been investigated as a therapy. The findings are mostly positive but have been made primarily in animal models, with some reports of null or adverse effect"
  • NAD+ to assess health in aging humans - AGING 2022, Vol. 14, Advance - "With NAD+involved in so many and such diversecellular functions, ranging from DNA repair tocircadian rhythms, redox reactions to cell division, inflammation to epigenetics [1, 2, 8], it could be argued that NAD+ plays a key role in the regulation of almostall biological processes. With NAD+ so convincingly linked to health in preclinical models [1], now demonstrated to reflect health in older humans [4], we ask ourselves the following: For any given intervention to significantly improve healthspan, should it not also serve to maintain NAD+ levels and homeostasis? We suggest that for a range of healthy aging interventions in humans—certainly including exercise—NAD+ abundance may serve as the best molecular marker tounderstand efficacy" - See NAD+ supplements at Amazpn.com.
  • Nicotinamide Mononucleotide Ameliorates Cellular Senescence and Inflammation Caused by Sodium Iodate in RPE - Oxid Med Cell Longev 2022 Jul 18 - "retinal pigment epithelium (RPE) ... The protective effects of NMN were demonstrated to rely on undisturbed Sirt1 signaling. Moreover, both the expression of senescence markers of RPE and subretinal inflammatory cell infiltration were decreased by NMN treatment in vivo. Our results indicate that RPE senescence induced by NaIO3 acquired several key features of AMD. More importantly, NMN may potentially be used to treat RPE senescence and senescence-associated pre-AMD changes by restoring the NAD+ levels in cells and tissues." - See NMN at Amazon.com.
  • Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study - Nutrients 2022 Feb 11 - "Deteriorating sleep quality and physical or mental fatigue in older adults leads to decreased quality of life and increased mortality rates. This study investigated the effects of the time-dependent intake of nicotinamide mononucleotide (NMN) on sleep quality, fatigue, and physical performance in older adults ... NMN (250 mg) or placebo was administered once a day for 12 weeks. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index. Fatigue was evaluated using the "Jikaku-sho shirabe" questionnaire. Grip strength, 5-times sit-to-stand (5-STS), timed up and go, and 5-m habitual walk were evaluated to assess the physical performance. Significant interactions were observed between 5-STS and drowsiness. 5-STS of all groups on post-intervention and drowsiness of the NMN_PM and Placebo_PM groups on mid- and post-intervention showed significant improvement compared with those in pre-intervention. The NMN_PM group demonstrated the largest effect size for 5-STS (d = 0.72) and drowsiness (d = 0.64). Overall, NMN intake in the afternoon effectively improved lower limb function and reduced drowsiness in older adults. These findings suggest the potential of NMN in preventing loss of physical performance and improving fatigue in older adults" - See NMN at Amazon.com.
    • NMN vs NR – 1 Huge Difference | Dr David Sinclair & Dr Andrew Huberman Interview Clips - YouTube - Dr. Sinclair, who had done significant research on NMN, claims MNM is better than the much more expensive NR. Dr. Sinclair makes sense. He confirms a lot of what I've read yet look how few views he gets compared to bullshit artists like Dr. Eric Berg or Dr. John Campbell. For some reason, whether it's politics or health, people prefer lies.
  • Nicotinamide riboside and caffeine partially restore diminished NAD availability but not altered energy metabolism in Alzheimer's disease - Aging Cell 2022 Jun 21 - "The redox co-factor nicotinamide adenine dinucleotide (NAD) declines with age, and NAD deficits are specifically associated with dysfunctional energy metabolism in late-onset Alzheimer's disease (LOAD). Nicotinamide riboside (NR), a dietary NAD precursor, has been suggested to ameliorate the aging process or neurodegeneration. We assessed whether NR with or without caffeine, which increases nicotinamide mononucleotide transferase subtype 2 (NMNAT2), an essential enzyme in NAD production, modulates bioenergetic functions in LOAD ... although NR and caffeine can partially restore diminished NAD availability, increasing NAD alone may not be sufficient to boost or restore energy metabolism in brain aging or alter aberrant energy management in LOAD. Nicotinamide riboside might still be of value in combination with other agents in preventive or therapeutic intervention strategies to address the aging process or age-associated dementia" - See nicotinamide riboside at Amazon.com.
  • Exercise increases the release of NAMPT in extracellular vesicles and alters NAD + activity in recipient cells - Aging Cell 2022 Jun 3 - "Aging is associated with a loss of metabolic homeostasis, with cofactors such as nicotinamide adenine dinucleotide (NAD+ ) declining over time. The decrease in NAD+ production has been linked to the age-related loss of circulating extracellular nicotinamide phosphoribosyltransferase (eNAMPT), the rate-limiting enzyme in the NAD+ biosynthetic pathway. eNAMPT is found almost exclusively in extracellular vesicles (EVs), providing a mechanism for the distribution of the enzyme in different tissues ... Here, we show that release of small EVs into the bloodstream is stimulated following moderate intensity exercise in humans. Exercise also increased the eNAMPT content in EVs, most prominently in young individuals with higher aerobic fitness. Both mature fit and young unfit individuals exhibited a limited increase in EV-eNAMPT release following exercise, indicating that this mechanism is related to both the age and physical fitness of a person. Notably, unfit mature individuals were unable to increase the release of eNAMPT in EVs after exercise, suggesting that lower fitness levels and aging attenuate this important signalling mechanism in the body. EVs isolated from exercising humans containing eNAMPT were able to alter the abundance of NAD+ and SIRT1 activity in recipient cells compared to pre-exercise EVs, indicating a pathway for inter-tissue signalling promoted through exercise. Our results suggest a mechanism to limit age-related NAD+ decline, through the systemic delivery of eNAMPT via EVs released during exercise"
  • CD38 inhibitor 78c increases mice lifespan and healthspan in a model of chronological aging - Aging Cell 2022 Mar 8 - "Nicotinamide adenine dinucleotide (NAD) levels decline during aging, contributing to physical and metabolic dysfunction. The NADase CD38 plays a key role in age-related NAD decline. Whether the inhibition of CD38 increases lifespan is not known. Here, we show that the CD38 inhibitor 78c increases lifespan and healthspan of naturally aged mice. In addition to a 10% increase in median survival, 78c improved exercise performance, endurance, and metabolic function in mice. The effects of 78c were different between sexes. Our study is the first to investigate the effect of CD38 inhibition in naturally aged animals" - See nicotinamide adenine dinucleotide at Amazon.com.
  • NAD + Metabolism in Cardiac Health, Aging, and Disease - Circulation 2021 Nov 30 - "Nicotinamide adenine dinucleotide (NAD+) is a central metabolite involved in energy and redox homeostasis as well as in DNA repair and protein deacetylation reactions. Pharmacological or genetic inhibition of NAD+-degrading enzymes, external supplementation of NAD+ precursors, and transgenic overexpression of NAD+-generating enzymes have wide positive effects on metabolic health and age-associated diseases. NAD+ pools tend to decline with normal aging, obesity, and hypertension, which are all major risk factors for cardiovascular disease, and NAD+ replenishment extends healthspan, avoids metabolic syndrome, and reduces blood pressure in preclinical models. In addition, experimental elevation of NAD+ improves atherosclerosis, ischemic, diabetic, arrhythmogenic, hypertrophic, or dilated cardiomyopathies, as well as different modalities of heart failure. Here, we critically discuss cardiomyocyte-specific circuitries of NAD+ metabolism, comparatively evaluate distinct NAD+ precursors for their preclinical efficacy, and raise outstanding questions on the optimal design of clinical trials in which NAD+ replenishment or supraphysiological NAD+ elevations are assessed for the prevention or treatment of major cardiac diseases. We surmise that patients with hitherto intractable cardiac diseases such as heart failure with preserved ejection fraction may profit from the administration of NAD+ precursors"
  • Preclinical and clinical evidence of NAD + precursors in health, disease, and ageing - Mech Ageing Dev 2021 Sep 10 - "NAD+ is a fundamental molecule in human life and health as it participates in energy metabolism, cell signalling, mitochondrial homeostasis, and in dictating cell survival or death. Emerging evidence from preclinical and human studies indicates an age-dependent reduction of cellular NAD+, possibly due to reduced synthesis and increased consumption. In preclinical models, NAD+ repletion extends healthspan and / or lifespan and mitigates several conditions, such as premature ageing diseases and neurodegenerative diseases. These findings suggest that NAD+ replenishment through NAD+ precursors has great potential as a therapeutic target for ageing and age-predisposed diseases, such as Alzheimer's disease. Here, we provide an updated review on the biological activity, safety, and possible side effects of NAD+ precursors in preclinical and clinical studies. Major NAD+ precursors focused on by this review are nicotinamide riboside (NR), nicotinamide mononucleotide (NMN), and the new discovered dihydronicotinamide riboside (NRH)" - See nicotinamide riboside at Amazon.com and nicotinamide mononucleotide at Amazon.com.
  • The balance between NAD + biosynthesis and consumption in ageing - Mech Ageing Dev 2021 Sep 9 - "Nicotinamide adenine dinucleotide (NAD+) is a vital coenzyme in redox reactions. NAD+ is also important in cellular signalling as it is consumed by PARPs, SARM1, sirtuins and CD38. Cellular NAD+ levels regulate several essential processes including DNA repair, immune cell function, senescence, and chromatin remodelling. Maintenance of these cellular processes is important for healthy ageing and lifespan. Interestingly, the levels of NAD+ decline during ageing in several organisms, including humans. Declining NAD+ levels have been linked to several age-related diseases including various metabolic diseases and cognitive decline. Decreasing tissue NAD+ concentrations have been ascribed to an imbalance between biosynthesis and consumption of the dinucleotide, resulting from, for instance, reduced levels of the rate limiting enzyme NAMPT along with an increased activation state of the NAD+-consuming enzymes PARPs and CD38. The progression of some age-related diseases can be halted or reversed by therapeutic augmentation of NAD+ levels. NAD+ metabolism has therefore emerged as a potential target to ameliorate age-related diseases. The present review explores how ageing affects NAD+ metabolism and current approaches to reverse the age-dependent decline of NAD+"
  • NAD + improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1/PGC-1α pathway - J Neuroinflammation 2021 Sep 16 - "Microglial-mediated neuroinflammation plays an important role in vascular dementia, and modulating neuroinflammation has emerged as a promising treatment target. Nicotinamide adenine dinucleotide (NAD+) shows anti-inflammatory and anti-oxidant effects in many neurodegenerative disease models, but its role in the chronic cerebral hypoperfusion (CCH) is still unclear ... NAD+ ameliorated cognitive impairment and dampened neuroinflammation in CCH models in vivo and in vitro, and these beneficial effects were associated with mitochondrial protection and ROS inhibition via activating Sirt1/PGC-1α pathway"
  • Nicotinamide mononucleotide supplementation enhances aerobic capacity in amateur runners: a randomized, double-blind study - See nicotinamide mononucleotide at Amazon.com - J Int Soc Sports Nutr 2021 Jul 8 - "Recent studies in rodents indicate that a combination of exercise training and supplementation with nicotinamide adenine dinucleotide (NAD+) precursors has synergistic effects. However, there are currently no human clinical trials analyzing this ... This study investigates the effects of a combination of exercise training and supplementation with nicotinamide mononucleotide (NMN), the immediate precursor of NAD+, on cardiovascular fitness in healthy amateur runners ... The participants were randomized into four groups: the low dosage group (300 mg/day NMN), the medium dosage group (600 mg/day NMN), the high dosage group (1200 mg/day NMN), and the control group (placebo) ... NMN increases the aerobic capacity of humans during exercise training, and the improvement is likely the result of enhanced O2 utilization of the skeletal muscle" - See nicotinamide mononucleotide at Amazon.com.
  • Progresses in both basic research and clinical trials of NAD+ in Parkinson's disease - Mech Ageing Dev 2021 May 11 - "The decline of nicotinamide adenine dinucleotide (NAD+) levels is a hallmark of aging in multiple organisms and tissues, including the human brain. Hence, agents that increase intracellular NAD + could have beneficial effects in aging and age-related neurodegenerative diseases. Disturbances in NAD + metabolism have also been observed in Parkinson's disease (PD), supporting a link between neuronal bioenergetics failure and disease pathogenesis" - See nicotinamide adenine dinucleotide at Amazon.com.
  • NAD + and NAFLD - Caution, Causality, and Careful Optimism - J Physiol 2021 May 1 - "The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide, and new treatments are direly needed. Nicotinamide adenine dinucleotide (NAD+ ) has been proposed as a potential target to prevent and reverse NAFLD. NAD+ is an important redox factor for energy metabolism and is used as a substrate by a range of enzymes, including sirtuins (SIRT), which regulates histone acetylation, transcription factor activity and mitochondrial function. NAD+ is also a precursor for reduced nicotinamide adenine dinucleotide phosphate (NADPH), which is an important component of the antioxidant defense system. NAD+ precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) are available as over-the-counter dietary supplements, and oral supplementation with these precursors increases hepatic NAD+ levels and prevent hepatic lipid accumulation in pre-clinical models of NAFLD. Moreover, NAD+ precursors were found to improve hepatic mitochondrial function and decrease oxidative stress in pre-clinical NAFLD models. NAD+ repletion also prevents NAFLD progression to non-alcoholic steatohepatitis (NASH), as NAD+ precursor supplementation is associated with decreased hepatic stellate cell activation, and decreased fibrosis. However, initial clinical trials have only shown modest effects when NAD+ precursors were administrated to people with obesity. We review the available pre-clinical investigations of NAD+ supplementation for targeting NAFLD, and discuss how data from the first clinical trials can be reconciled with observations from preclinical research" - See nicotinamide adenine dinucleotide at Amazon.com.
  • Effect of coenzyme Q10 plus nicotinamide adenine dinucleotide supplementation on maximum heart rate after exercise testing in chronic fatigue syndrome - A randomized, controlled, double-blind trial - Clin Nutr. 2016 Aug;35(4):826-34 - "80 CFS patients assigned to receive either CoQ10 plus NADH supplementation or matching placebo twice daily ... The CoQ10 plus NADH group showed a significant reduction in max HR during a cycle ergometer test at week 8 versus baseline (P = 0.022). Perception of fatigue also showed a decrease through all follow-up visits in active group versus placebo (P = 0.03). However, pain and sleep did not improve in the active group. Coenzyme Q10 plus NADH was generally safe and well tolerated" - [Nutra USA] - See ubiquinol products at Amazon.com and nicotinamide adenine dinucleotide at Amazon.com.
  • Is NADH effective in the treatment of Parkinson's disease? - Drugs Aging. 1998 Oct;13(4):263-8
  • NADH stimulates endogenous dopamine biosynthesis by enhancing the recycling of tetrahydrobiopterin in rat phaeochromocytoma cells - Biochim Biophys Acta. 1997 Jul 10;1361(1):59-65
  • Current therapy of idiopathic Parkinson disease. 2: Recent and alternative therapies - Fortschr Med. 1997 May 10;115(13):37-41
  • Parenteral application of NADH in Parkinson's disease: clinical improvement partially due to stimulation of endogenous levodopa biosynthesis - J Neural Transm. 1996;103(10):1187-93 - "In conclusion NADH in used galenic form may be a potent stimulator of endogenous levodopa biosynthesis with clinical benefit for Parkinsonian patients."
  • Stimulation of dopamine biosynthesis in cultured PC 12 phaeochromocytoma cells by the coenzyme nicotinamide adeninedinucleotide (NADH) - J Neural Transm Park Dis Dement Sect. 1993;5(2):147-56
  • Nicotinamide adenine dinucleotide (NADH)--a new therapeutic approach to Parkinson's disease. Comparison of oral and parenteral application - Acta Neurol Scand Suppl. 1993;146:32-5
  • Kynurenine pathway abnormalities in Parkinson's disease - Neurology. 1992 Sep;42(9):1702-6